Allergic reactions include four types of reactions, i.e., types I, II, III and IV. The type I (immediate-type, anaphylactic) allergic reaction is triggered by the reaction-relating-factor immunoglobulin E (hereinafter abbreviated as an IgE antibody). The reaction steps can be divided roughly into the following three steps. The first step is a sensitization step involving IgE antibody production and binding of the resulting IgE antibodies to mast cells or basophils. The second step involves degranulation of the mast cells or basophils and release of chemical mediators. The third steps involves onset of effects of the released chemical mediators on the target organs. Thus, the type I allergic reaction against foreign antigens leads to onset of symptoms through the above reaction steps.
Only symptomatic treatments by inhibiting the above second and/or third reaction steps have been carried out to treat allergic diseases. That is, the treatments are carried out by inhibiting the release of chemical mediators accompanying the degranulation and/or by inhibiting allergic reactions induced by the released chemical mediators. These symptomatic treatments have been known to be effective not only in systemic administration of anti-allergic agents but also in their topical administration to the nose, etc. However, the effects of the treatments are limited because the treatments do not inhibit IgE antibody production which is the basic first step of the type I allergic reaction.
As fundamental remedies against the type I allergic reaction, medicaments inhibiting the above first step, namely IgE antibody production inhibitors, are being developed. Examples of such inhibitors include {2-4-(3-ethoxy-2-hydroxypropoxy)phenylcarbamoyl!ethyl}dimethylsulfonium p-toluenesulfonate (suplatast tosilate, hereinafter sometimes referred to as Compound A), and ethyl 2,6-bis-(N-methylcarbamoyl)-pyridine-4-carboxylate (hereinafter sometimes referred to as CS-1433). Anti-allergic effects in their systemic administration, namely oral administration, etc., have been reported (JP-A 59-167564, New Current, Vol. 3, No. 26 (1992) etc. for Compound A; Japanese Journal of Allergology, Vol. 36, No. 8 (1987) etc. for CS-1433). Regarding ophthalmic topical administration of Compound A, etc., anti-allergic effects of eye-dropping, etc., of Compound A are reported (EP-A-624,367, etc.).
However, because the mechanisms of nasal topical IgE antibody production are not clear, there is no report on effects of nasally topically administered drugs applicable to nasal topical membrane allergic reaction.
As described above, there is no satisfactory anti-allergic pharmaceutical compositions that are effective and safe in nasal topical administration. The object of the present invention is to provide an excellent anti-allergic pharmaceutical composition for nasal topical use.